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Dibenzocycloheptene antidepressants are tricyclic antidepressants (TCAs) that contain the dibenzocycloheptene moiety in their chemical structures. They are used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Herein, we report the synthesis of a pure tricyclic antidepressant containing dibenzocycloheptene moiety named N-(5H-dibenzo[a,d][7]annulen-5-ylidene)-2-methylpropane-2-sulfinamide (3) in high chemical yield through condensing (R)-tert-butanesulfinamide with a dibenzosuberon ketone. Its structure is elucidated by employing the X-ray technique, NMR spectroscopy characterization, and DFT calculations at the B3LYP/6-31++G(d,p) level of theory. The geometrical parameters are relatively well reproduced, and the optimized and X-ray geometries are relatively well superimposed. The interconnects in the crystalline form of 3 were identified through the analysis of its Hirshfeld surface (HS) and fingerprint plots. The highest interatomic contacts were found between H...H of 58.2% and C.H of 30.6%. Further, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) pharmacokinetics, and physicochemical properties of 3 were determined, which showed that 3 may act as a carbonic Anhydrase I inhibitor. The binding affinity of 3 into the binding site of carbonic Anhydrase I is investigated using a molecular docking study. It forms a stable complex into the binding site of CA I with a binding energy of −7.12 kcal/mol. [ABSTRACT FROM AUTHOR]

In this work, theoretical and experimental studies of a new Indazole derivative named 2-(5-nitro-1-H-indazol-1-yl) acetic acid (3), including the synthesis and characterization by 1H and 13C-NMR, FT-IR, UV spectroscopies are reported together with its X-ray crystal structure. The compound crystallizes in the monoclinic crystal system of P21/c space group and unit cell constants: a = 7.8541(10) Å, b = 7.9274(11) Å, c = 15.877(2) Å, β = 101.149(5)°. In the crystal, O–H···N and C–H···O hydrogen bonds form a 3-D network structure containing small channels running parallel to the b-axis. B3LYP/6-311++G** calculations in the gas phase and ethanol solution suggest the existence of C1 and C2 conformers where the structure of C1 in both media is in agreement with that observed by X-ray diffraction. Probably, the high values observed in the dipole moments of C1 justify its presence in gas and solution phases. The stabilities of both forms were justified by NBO and AIM calculations where C1 is more stable than C2. C1 shows a higher solvation energy, dipole moment, and higher hydration than C2 while the frontier orbitals suggest a higher reactivity of C1 over C2. Force fields and complete vibrational assignments were performed for the C1 conformer because it was detected in the solid phase. Scaled force constants for both forms are also reported. Calculated chemical shifts for (3) are consistent with the experimental 1H and 13C-NMR spectra in the DMSO-d6 solution. The anti-COVID activity of 3 is investigated by its molecular docking into the binding site of SARS CoV-2 3CLpro (3 C-like protease). It shows a moderate binding affinity into the binding site of 3 C-like protease with a maximum binding energy of −5.57 kcal mol−1. [ABSTRACT FROM AUTHOR]

AbstractIn the present work, five pyrazole-hydrazone biomolecule ligands (L1–L5) were synthesized by condensation between 1H-pyrazole-3-carbohydrazide (2) and aromatic benzaldehydes. Their corresponding structures were elucidated employing NMR and FT-IR spectra and ESI-MS data. Li-Cu(II) complexes (i = 1–5) were evaluated for catecholase activity in situ at standard conditions. The findings disclose that the catecholase oxidation rate varies with the substituted functional groups in ligand and the anion type in the copper (II) salt. Catecholase activity results showed that the L(i = 1–5) -Cu(II)SO4 complexes exhibited efficient catalytic activity, and a maximum activity of 105 ± 42 µM.min−1 is obtained with L5-Cu(II)SO4. DFT and NBO calculations have been carried out to identify the global reactivity and the strength of interaction bonds between the donors and acceptors in L1–L5. The optimized structure of L1–L3 and L5 were found planar, while that of L4 is out of the molecular plan and forms a torsion angle of 18 degrees due to the presence of methoxy and hydroxyl group at meta and para. In L4, the 5-methyl-1H-pyrazole moiety. NBO findings show that the strongest interactions in L1–L5 are those involved in the electronic transition from π-bonding → π*-antibonding and LP → π*- antibonding molecular orbitals. Further, the anti-SARS-CoV-2 of L1–L5 are investigated by estimating their binding affinities into its binding. The docking results reveal that L1–L5 may act as SARS-CoV-2 main protease inhibitors with estimated binding energies in the −6.00 to −8.0 kcal.mol−1 range. [ABSTRACT FROM AUTHOR]

Pyrazolones derivatives are known for their pharmaceutical and therapeutic activities. In this regard, some new pyrazolone derivatives have been synthesized using cyclocondensation, nucleophilic substitution, and alkylation reactions. Their corresponding structures were elucidated using X-ray diffraction and NMR spectroscopic techniques. The experimental spectral data were compared with the predicted ones obtained at the B3LYP/6-311++G(d,p) level of theory. Geometrical parameters and chemical shifts are relatively well reproduced with correlation coefficients higher than 90%. The intercontacts in crystal units were investigated by the analysis of their corresponding Hirshfeld surfaces and fingerprint maps, which reveal that the major contacts are found for H...H intercontacts. Finally, the inhibition efficiency of the novel pyrazolone derivatives as SARS-CoV-2 Mpro is estimated by determining their binding affinities into the binding site of SARS-CoV-2 Mpro. The docking results reveal that the current pyrazolone derivatives may act as potent inhibitors of SARS-CoV-2 Mpro and that their inhibition efficiency may be strongly influenced by the substituted functional groups of pyrazolone moiety. Synthesis of new 4-Substituted Pyrazolone derivatives Good correlations are obtained between the spectra and X-ray data with the predicted ones. Hirshfeld surface analysis is used to analyze intermolecular interaction. 3D molecular structure is characterized using x-Ray and spectroscopic techniques. Interactions for of the newly synthesized compounds 2b, 3b, 3a, and 4 docked SARS-CoV-2 Mpro/PDB: 6LU7-A chain protein. [ABSTRACT FROM AUTHOR]

Two novel N-alkylated isatin derivatives (2–3) were synthesized under phase-transfer catalysis conditions. Their condensation with hydrazine hydrate and phenylhydrazine in refluxing ethanol as solvent generates two series of isatin derivatives (3-hydrazono and 3-phenylhydrazono) (4–7). The structures synthesized are elucidated using UV/Vis, FTIR, 13C-NMR, 1H-NMR, and single crystal X-ray diffraction techniques of 2, 3, and 5. The experimental data were compared with the predicted ones obtained at the B3LYP/6-31G(d,p) level of theory. Relatively, good agreements were found between the calculated and experimental results. The intermolecular contacts in 2, 3, and 5 were investigated through the Hirshfeld surface analysis. The expected inhibitory efficiency of 2, 3, and 5 against cyclooxygenase-2 (COX-2) are investigated by their molecular docking into the binding site of COX-2, which revealed that 2 might have strong inhibition efficacy against COX-2 compared to 3. [ABSTRACT FROM AUTHOR]

A novel series of benzofuran-pyridazine derivatives have been synthesized and characterized by different spectroscopic techniques including FT-IR, 1H-NMR, 13C-NMR, and ESI-MS spectrometry. All synthesized compounds were evaluated in vitro for their antidiabetic activity against α-glucosidase and β-galactosidase enzymes. All derivatives (3a-3h) and (4a-4b) showed a remarkable inhibitory potential greater than 89% against α-glucosidase enzyme compared to standard acarbose (42.50%), and compounds 3 b and 4a exhibited significant inhibitory potential against β-galactosidase enzyme with 50.33% and 57.67% respectively, compared to standard Queretin (52.00%). A molecular docking study was conducted to understand the binding interactions of the compounds with the active site of the α-glucosidase enzyme. [ABSTRACT FROM AUTHOR]

There is an excellent approach to design antidiabetic drugs based on inhibitors of α-glucosidase. These inhibitors control the sugar level in blood of diabetic patients to avoid complications on patient health. In current study we designed a new series of oxadiazole based derivatives (1–20). All synthesized analogues were characterized through 1H-NMR, 13C-NMR, HREI-MS and evaluated against α-glucosidase inhibitory potential and analogues 1, 4, 16, 17, and 19 showed excellent activity ranging 1.10–8.60 μM. The analogues 2, 3, 5, 6, 10, 14, and 18 showed 4 to 2 folds better activities ranging 10.10–21.30 μM than standard drug standard acarbose (IC50 = 38.40 ± 0.80 μM). The analogues 11, 13, and 20 showed activities ranging 34.30–34.60 μM better than standard. The analogues 7, 12, and 15 showed weak activities. The analogues 8 and 9 found completely inactive. The binding interactions of these active derivatives were confirmed through molecular docking. The docked analogues, and the α-glucosidase exhibited negative bending energies. The inhibition of α-glucosidase via tested analogues were thermodynamically favored. Based on these results, analog 1 was evaluated against STZ induced diabetic rats and found potent at a dose of 200 mg/kg. [ABSTRACT FROM AUTHOR]

Herein, new quinazoline derivatives were synthesized via efficient S-arylation, requiring only two steps and few reactants. As-obtained compounds named as 2-(4-fluoro-benzylsulfanyl)-3-(4-substitued)-6-methyl-3H-quinazolin-4-one were characterized by FTIR and NMR spectroscopy, as well as DFT calculations. The new quinazoline derivatives were prepared as drug-like molecules to assess their potential as antibacterial agents. Biological tests revealed that these derivatives exhibit interesting activities against several bacterial strains. Docking studies were conducted: Conventional intermolecular hydrogen bonds are observed between the docked compounds and the active site of the target enzyme. Our experimental results (in vitro study) were in agreement with those obtained from docking studies as the as-prepared compounds exhibited the highest docking result and simultaneously demonstrated promising antibacterial activity. [ABSTRACT FROM AUTHOR]

Two N-isonicotinoyl arylaldehyde hydrazones named N'-(4-fluorobenzylidene)isonicotinohydrazide (2a) N'-(4-methylbenzylidene)isonicotinohydrazide (2 b) have been synthesized and characterized utilizing spectroscopic techniques and X-ray diffraction. The s-cis isomeric geometry of 2a and 2 b is confirmed by comparing the observed stretching bond of the azomethine group with their corresponding calculated ones of s-cis and s-trans isomers for both 2a and 2 b. The s-cis geometry is in good accordance with the one obtained by X-ray techniques. The global and local electronic properties of 2a and 2 b were determined at the B3LYP/6-311 + G(d,p) level of theory. The Results reveal that the stability of s-cis isomers compared to s-trans ones is mainly refer to the intramolecular carbon-hydrogen bonding formed between lone pairs of the carbonyl group and the hydrogen atom of azomethine of 2.15 Å. The antidiabetic activity of 2a and 2 b is investigated by determining their potency to inhibit α-glucosidase. 2a and 2 b showed higher inhibitory toward α-glucosidase as compared to the reference drug acarbose. Molecular docking of 2a and 2 b into the active site of α-glucosidase showed that the higher inhibition efficiency of 2 b compared to 2a is mainly refers to the stability of 2 b-(α-glucosidase) complex compared with 2a-(α-glucosidase). [ABSTRACT FROM AUTHOR]

Oxadiazole-based-thiourea analogs (1–18) were synthesized and evaluated for their β-glucuronidase inhibitory activity. All analogs showed extensive β-glucuronidase inhibitory potential ranging between (IC50 = 2.20 ± 0.01 µM) to (IC50 = 52.25 ± 1.20 µM) by comparing with the standard D-Saccharic acid 1,4-lactone (IC50 = 48.30 ± 1.25 µM). Among the series, analogue 7 having IC50 value (IC50 = 2.20 ± 0.01 µM)), 16 (IC50 = 4.40 ± 0.10 µM) and 4 (IC50 = 9.20 ± 0.20 µM) showed an excellent inhibitory potential greater than that of standard D-saccharic acid-1,4- lactone. Analogue 7 (IC50 = 2.20 ± 0.01 µM) of this series having flouro group at ortho-position of phenyl ring was recognized to be most active analogue due to involvement of flouro group in hydrogen bonding with the enzyme active site. In addition, all synthesized derivatives characterized by using High Resolution Mass Spectrometry (HR-MS), 13C-NMR and Nuclear Magnetic Resonance Spectroscopy (1H-NMR proton). For better understanding of binding mode of interactions of these active analogs molecular docking study was performed. Structure Activity relationship (SAR) was also discussed. [ABSTRACT FROM AUTHOR]

The Juglans regia root aqueous extract (JRRAE) phytochemical variability and the investigation of their antimicrobial, antibiofilm, insecticidal, and anti-leishmanial properties were studied. As a result, the JRRAE chemical profile revealed the presence of biomolecules using UV, HPLC, and FT-IR analysis. The investigations showed marked antibacterial activities, highlighted inhibited biofilm formation, induced lethality Leishmania amazonensis promastigotes (50%), and possess an insecticidal activity at 100 µg/ml. A molecular docking study was performed against S. aureus gyrase, S. aureus tyrosyl-tRNA synthetase, human peroxiredoxin 5, cyclooxygenase-2, and trypanothione reductase and confirmed that the activities are mainly due to coumarin, epicatechin, juglone, epicatechin, and epicatechin presence, respectively. The stability of these complexes is essentially related to the strong hydrogen bonds formed between the most active compounds and the binding site amino acids. The identified compounds were found to pass the absorption, distribution, metabolism, and excretion property as well as five Lipinski's rules with good drug-likeness and pharmacokinetic behavior. [ABSTRACT FROM AUTHOR]

An efficient pathway was disclosed for the synthesis of 3-chloro-6-nitro-1H-indazole derivatives by 1,3-dipolar cycloaddition on dipolarophile compounds 2 and 3. Faced the problem of separation of two regioisomers, a click chemistry method has allowed us to obtain regioisomers of triazole-1,4 with good yields from 82 to 90% were employed. Also, the antileishmanial biological potency of the compounds was achieved using an MTT assay that reported compound 13 as a promising growth inhibitor of Leishmania major. Molecular docking demonstrated highly stable binding with the Leishmania trypanothione reductase enzyme and produced a network of hydrophobic and hydrophilic interactions. Molecular dynamics simulations were performed for TryR-13 complex to understand its structural and intermolecular affinity stability in a biological environment. The studied complex remained in good equilibrium with a structure deviation of ~1-3Å. MM/GBSA binding free energies illustrated the high stability of TryR-13 complex. The studied compounds are promising leads for structural optimisation to enhance the antileishmanial activity. [ABSTRACT FROM AUTHOR]